Antitumour activity of synthetic curcuminoid analogues (1,7-diaryl-1,6-heptadiene-3,5-diones) and their copper complexes

Abstract

Four new curcuminoid analogues, 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione, 1a; 1,7-di(2-furyl)-1,6-heptadiene-3,5-dione, 1b; 1,7-di(2-naphthyl)-1,6-heptadiene-3,5-dione, 1c; 1,7-bis(2-chlorophenyl)-1,6-heptadiene-3,5-dione, 1d; and their copper(II) complexes of ML 2 stoichiometry were synthesized and characterized by UV, IR, 1 H NMR, ESR and mass spectral data. The compounds were investigated for their possible cytotoxic and antitumour activities. It was found that copper chelates are remarkably active compared with free curcuminoid analogues. All the compounds were found to be cytotoxic towards Ehrlich ascites carcinoma cells and cultured L929 (lung fibroblast cells). In the case of culture studies, concentrations needed for 50% cell death were around 5 µg/ml for copper complexes and 10 µg/ml for curcuminoid analogues. Copper complex of 1a with hydroxyl group in the phenyl ring was found to be most active towards L929cells (1 µg/ml produced 43.3 ± 1.3% cell death). Compound 1b, which possesses a furyl ring system, was found to show least activity towards increase in life span of tumour-bearing mice (increase in life span 39.31%). Copper chelates of all curcuminoid analogues showed a significant reduction (p < 0.001) of solid tumour volume in mice.

Curcumin and cyclopalladated complexes: A recipe for bifunctional biomaterials

“…Recently the study of the mechanism of their chemiopreventive activity has attracted increasing attention [13][14][15][16][17]. Although b-diketones are known to form complexes with almost every metal, few metal complexes of curcumin and its derivatives have been reported [18], most of which are based on bis M(curc) 2 , M@VO, Cu(II), Ni(II) and Co(II) or tris M(curc) 3 M@Ga(III) and In(III), for evaluation as anticancer agents in vitro and in vivo [19][20][21][22][23].…”

Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

“…The human glioblastoma U-87 and lung carcinoma A549 cells were found to be less sensitive. John and coworkers [109] have synthesized copper complexes of four new Curcumin analogs (149-152) wherein the metal complexes were found to be remarkably active.…”

Unsaturated polycarbonyl compounds and their metal complexes

“…Biological studies. Unsaturated β-dicarbonyl compounds such as curcuminoids are known to possess antifungal and antimicrobeal activities in addition to their numerous biological significance [1][2][3][4][5][6][7]20]. Since the unsaturated β-ketoanilides are structurally related to curcuminoids, the antifungal activity of these compounds and their typical metal complexes were also studied by disk diffusion technique [21] using agar nutrient as the medium.…”

“…Curcuminoids, a group of structurally related 1,3-dicarbonyl compounds in which the keto groups are directly linked to olefinic carbons, constitute the major physiologically active principle of the traditional Indian medicinal plant turmeric (Curcuma longa, Linn, Zingiberacea family) and several other related species of wide pharmacological interest [1,2]. These natural curcuminoids, their synthetic analogues and their metal complexes are known to exhibit anticancer [1][2][3][4][5], antioxidant [4,6] and anti-inflammatory [7] activities.…”

“…These natural curcuminoids, their synthetic analogues and their metal complexes are known to exhibit anticancer [1][2][3][4][5], antioxidant [4,6] and anti-inflammatory [7] activities. The alkenyl linkage appears to be a major factor in determining their biological properties.…”